Role of general practitioners in prevention and treatment of hepatitis B in China

Hangzhou,China

Introduction

Hepatitis B virus (HBV) infection affects over two billion individuals in the world.[1]Although hepatitis B vaccines have been used since 1982,there are still 350-400 million chronic carriers,of whom 75% are in Asia.[1]A recent sero-epidemiological survey[2,3]revealed that the HBsAg carrier rate in the general population was 7.18%.The complications of patients with chronic hepatitis B (CHB) include hepatic decompensation,cirrhosis and hepatocellular carcinoma(HCC),which result in one million deaths annually.[4]HBV infection is still very serious in China.

Since there is no curative method for CHB,effective prevention and control are crucial.In China,specialists in infectious diseases,gastroenterologists,hepatologists and general practitioners (GPs) are often involved in the management of CHB.But there are no standardized therapeutic protocols and therefore problems occur in the treatment of CHB.The development of a reasonable and effective approach to prevent and cure HBV infection is of particular importance.Thus,the role of GPs in the management of CHB infection is increasingly important.In the present article,we reviewed the current status of prevention and treatment of HBV infection in China and evaluated the function of GPs in the management of CHB.

Current attitudes of GPs towards the management of patients with CHB

CHB is defined variably in different countries or regions,but it is documented as a notifiable disease in all countries.The system for the management of CHB in the world is different.In European countries,GPs are responsible for the diagnosis and treatment of patients with CHB.Only when the practitioners have difficulties in dealing with CHB patients,these patients may be referred to specialists in infectious diseases,gastroenterologists or hepatologists.[5]In Canada,GPs are also responsible for the diagnosis and treatment of CHB patients according to the clinical guidelines formulated by the specialty societies.[6]Because of the lack of training in the diagnosis and treatment of CHB,GPs in some countries like India,Australia,Malaysia and China (such as the regions Hong Kong and Taiwan) are often reluctant to deal with CHB patients,rather refer the patients to a specialist in thisfield.In China,CHB patients are usually treated in the hospitals specialized in infectious diseases.Although GPs have prescription rights,clinics and community health service institutions are not equipped with appropriate testing equipments and therapeutic agents.Therefore,GPs in China are often reluctant to provide services to CHB patients.[7]

Role of GPs in dealing with CHB patients

The role of GPs in hepatitis B vaccine project

HBV immunization is the most effective way for the prevention of HBV transmission.A national survey[8]of China showed that the efficacy of hepatitis B vaccination at birth was 88.3%.With the introduction of hepatitis B vaccination,the prevalence of HBsAg has reduced to 1.0% in children born after 1999 and 2.1% in all children.Although routine vaccinations for infants,[9]adolescents[9]and high-risk populations[10]could successfully reduce the incidence of HBV infection,many factors may constrain the vaccination rate.These factors could be categorized into two types.First,children of 5 years or older,rural residents in Western China,those who are born at a township hospital or at home,and ethnicities such as Tibetan or Uygur nationalities.[8,11]Second,lack of knowledge,stigma,financial barriers,provider knowledge,language barriers,cultural differences,complementary and alternative medicine(CAM),and community buy-in.[12-23]Takahashi et al[24]reported that most people get knowledge about HBV transmission from their physicians.Therefore,GPs need to make great efforts to educate the people and to increase the immunization rate.

Apart from the efforts from GPs,the local government should take actions.For example,CHB patients have disadvantages in job hunting,etc.,this deters the individuals at risk from getting screened (even if screening is available in some regions) and subsequently lowering the vaccination rate.In an effort to preclude the HBV-related bias,the Ministry of Health of China,Ministry of Human Resources and Social Security co-issued a notice in 2007,stating that an employer shall not dismiss an HBV carrier simply because of his/her infection.[25]Two years later,the Ministry of Health further announced that the healthcare institutions are prohibited to expose HBV testing results to the employers or school recruiters,indicating greater progress infighting discrimination.[26]Up to now,the new policy is of significant effectiveness.However,GPs and the local authorities still have a lot to do in the improvement of CHB testing and vaccination rates.

Hepatitis B vaccine is given mainly to newborns,infants,unimmunized young children under age of 15 years.However,recent studies[27,28]revealed that traditional vaccination coverage is not enough.Hence,the Center for Disease Control (CDC) of the USA recommended that all healthcare providers and students should receive hepatitis B vaccine.[29,30]To expand vaccination coverage,we have implemented a comprehensive program for both infants and adults in 2011,which is called "2011 Program".[31]The program is designed for both infants and adults who were born before 1992 and were not covered under the national HBV vaccination program in 2011 in 12 counties of Zhejiang province.The adults were given with a high dose of vaccine (10 μg) recommended by the National Expert Panel for the Mega-Project for National Science and Technology Development.Infants were given the vaccine on the same schedule suggested by the earlier program.

The above measures could greatly increase the vaccination rates in the country.The GPs involvement in vaccination planning,correct vaccine inoculation,fully immunized improvement and later follow-up,and most importantly the health education will help to increase the vaccination rates.The specialists in infectious diseases and GPs from 12 counties of Zhejiang province have participated in HBV vaccination and community education,the latter could greatly improve the knowledge of the public on CHB.[32]

Role of GPs in interrupting the transmission

HBV as a blood-borne pathogen is primarily transmitted via mother-to-child exposure,sexual intercourse,close household contact,needle-sharing,and occupational (healthcare-related) exposure.[33]Whereas in China,vertical transmission at childbirth is the predominant route of chronic infection.[34,35]Therefore,interrupting the vertical transmission can decrease the HBV infection.Post-exposure prophylaxis (PEP) initiated at birth is recommended for all infants whose mothers have been infected by HBV.[11]A combination of hepatitis B immune globulin and an accelerated course of HBV vaccine after PEP has been effective to prevent perinatal HBV transmission in almost 90% of the cases.[36]Most countries including China have introduced routine preconception HBsAg-screening of all pregnant women and maximize opportunities to prevent the mother-tochild transmission of HBV.[37]Since CHB patients and HBV carriers are important sources of infection,GPs in China will respond to the community registered hepatitis B patients or carriers by regular follow-up and dessiminating preventive knowledge especially to pregnant women or patient's family,and perform regular examination for timely detection and effective control of HBV infection according to the principles and protection standards for the control of hospital infection.In fact,we have educated GPs from almost all counties of Zhejiang province how to follow up the patients and how to educate the community regularly.To make the health education more effective,we distribute educational pamphlets to the GPs in the province.

Besides GPs' efforts,patients should also make some precautions.First of all,personal hygiene should be strongly emphasized.They should avoid sharing razors,dental equipments and other items.Sex education is also important.Sexual partners of HBsAg-positive individuals should receive vaccination or use condoms,and those with uncertain health conditions must use condoms.HBsAg-positive pregnant women should be vaccinated according to the schedule before their labor.

Role of GPs in the treatment

GPs involvement is cost-effective not only in the prevention by vaccination but also in the diagnosis and treatment of HBV-related liver diseases.A recent study on inpatients with HBV-related diseases who were treated from April 2010 to November 2010 revealed that the direct cost for CHB and its complications was up to $4552 and $24 973,respectively.[38]GPs,as primary healthcare workers,provide prompt service to the patients with CHB.Their involvement in the treatment of patients with CHB is of great importance as in a long run it prolongs patient life span,improves life quality,and reduces the economic burden of patient's family.

Two main therapeutic strategies are available for hepatitis "e" (HBe) antigen-positive (HBeAg+ve) or antigen-negative (HBeAg-ve) CHB patients.They are effective to achieve and maintain viral suppression.The 1-year treatment is prescribed with interferon alpha(IFN)/pegylated IFN (PEG-IFN),but the long-term treatment is given with nucleotide analogues (NAs).[39]Other treatments available in China include traditional Chinese herbal medicines and others.[40]However,each of them has advantages and disadvantages,which need to be carefully tailored for individual patients.GPs are able to guide patients to seek appropriate and efficacious treatment regimens.GPs in local communities perform detailed laboratory examination for their CHB patients,and discuss with patients the condition of their diseases and suitable therapeutic modalities.Through appropriate training,GPs are able to offer drug therapy.Since 2005 as a health project,the residents of Zhejiang province have been subjected to health check up every two years free of charge so as to effectively screen and manage CHB patients.The project includes physical examination and routine laboratory testing.With the support of the Mega-Project for National Science and Technology Development for the "11th Five-Year Plan of China" and Health Bureau of Zhejiang Province,HBsAg test and alanine aminotransferase (ALT) assay were added to the health project in 2010.[31]

GPs in the community management of CHB

The management of CHB patients is to reduce HBV infection and to prevent hepatitis B complications.This needs close cooperation between GPs and CHB patients.Once CHB patients or carriers are diagnosed in communities,GPs will report them to the CDC,and get the patients registered.At the same time,GPs advise the family members of the patients to test serum HBsAg,anti-HBc and anti-HBs or have the suspected (all three markers are negative) vaccinated.GPs also need to follow up the registered patients and carriers and educate the patients and their family members.[41]

In recent years,GPs involvement in the management of CHB patients has been popularized in many parts of China.Zhang et al[42]reported the role of GPs in the community management of CHB patients.All GPs should be trained for two years via a comprehensive hospital-community intervention program of CHB.The community management program for CHB includes education,consultation,follow-up,psychological guidance,laboratory examination and referral services.GPs are benefited from this program and know their role in the management and monitoring of CHB patients,i.e.,they know how to follow up or monitor the patients,and when to do consultation and referral.The results of health check-up according to the health project in 2010 version are entered in the Electronic Health Records (EHR) system and the records are managed by physicians including GPs in the community.[31]

Problems GPs encountered in the prevention and control of hepatitis B

In recent years,GPs involvement in the management of patients with CHB has achieved promising initial results.However,there are many issues GPs encountered during implementation of this program.[43]

Shortage of experience

Chao et al[44]reported that some healthcare providers including GPs do not have sufficient knowledge on HBV and HBV-related diseases,especially among health workers from rural areas.Even though a large number of GPs,particularly community GPs have received training before doing prevention and control work.

Shortage of manpower and strong project intensity

According to our own preliminary research unpublished,each GP in 50% of the communities has to deal with more than ten CHB patients,including laboratory diagnosis,treatment,follow-up,family prevention,vaccination and others.However,many people still have no access to GP in their communities.Hence the shortage of GPs significantly limit the implementation of the health project.Additionally,the lack of knowledge about hepatitis B prevention and management in residents also increases the burden of GPs,leading to 20% of GPs out of the involvement.

Lack of examination equipments and therapeutic drugs

In China,GPs involvement in hepatitis B prevention and control is mostly performed in community health service centers.Most centers only provide limited services such as tests of liver function and routine blood,whereas they have no capacity to detect hepatitis B related antigens and antibodies,direct bilirubin,indirect bilirubin and hepatitis B virul load.Therefore,insufficient data could not make a correct diagnosis of hepatitis B.Moreover,community centers do not have all types of effective but expensive anti-HBV drugs which hinder the immediate treatment of CHB patients.Therefore,without the support of other institutions,GPs are unable to independently complete the program of hepatitis B prevention and control.[45]

No uniformed standards and approaches

The involvement of GPs in the hepatitis B prevention and control is a novel experience.But there are no universally recognized standards or post-management guidelines.In clinical practice,GPs may encounter uncharted scenarios which could not be managed without definitive guidelines of management.

Recommendations

GPs training for prevention and control of hepatitis B

A 6-year study reported that the training of GPs of village clinics in Hebei province improved their practice,for instance,the sterilization of needles,syringes and transfusion sets.The HBV carrier rate of 2-year-old children (mothers are HBsAg negative) dropped from 11.6% to 2.1%,which indicates that the training of GPs decreases the transinfection rate of HBV.[46]With the increasing demands on community health,the Chinese government should increase thefinancial support for GP training.These measures combined with bi-annual retraining and an assessment system will improve the professional level of GPs,who can practice according to the guidelines for the prevention and treatment of CHB.[47,48]

Increased funding for community management of hepatitis B

The Chinese government should increase the funding for community-based management of CHB patients,deploy HBV-related laboratory testing equipments and therapeutic drugs,or give appropriate subsidies for CHB patients.The management of CHB patients should be included in GP evaluation.On the one hand,the full involvement of GPs in the management of CHB patients will help reduce the economic burden of patients and enforce their adherence to CHB treatment.

The prevention and treatment of CHB in China still has a long way to go.China has a high incidence of CHB,and GPs are at the fulcrum of community health services and play a crucial role in the prevention and treatment of CHB.

Conclusion

Hepatitis B virus infection is common in China,and it is associated with considerable economic burden to patients and their families as well as a high liver-related morbidity and mortality.Although the role of GPs is increasingly important,the role in the management of CHB needs to be clarified.The community has no established procedure for the prevention and control of hepatitis B and there is little awareness from GPs to participate in this project.Therefore,expansion of GPs with appropriate training should play an important role in the prevention and control of CHB.

Contributors:RJJ contributed to the design and conduct of this study,preparation of this manuscript and the study conception.WB and YJ contributed to critical review of the manuscript.All authors contributed to the design and interpretation of the study and to further drafts.LLJ is the guarantor.

Funding:This study was supported by a grant from the National Scientific and Technological Major Project of China (2013ZX10004 904-001-005).

Ethical approval:Not needed.

Competing interest:No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

1 Liaw YF,Chu CM.Hepatitis B virus infection.Lancet 2009;373:582-592.

2 Liang X,Bi S,Yang W,Wang L,Cui G,Cui F,et al.Epidemiological serosurvey of hepatitis B in China--declining HBV prevalence due to hepatitis B vaccination.Vaccine 2009;27:6550-6557.

3 Lu FM,Zhuang H.Management of hepatitis B in China.Chin Med J (Engl) 2009;122:3-4.

4 Chen SJ,Zhao YX,Fang Y,Xu WZ,Ma YX,Song ZW,et al.Viral deletions among healthy young Chinese adults with occult hepatitis B virus infection.Virus Res 2012;163:197-201.

5 McMahon BJ.Implementing evidenced-based practice guidelines for the management of chronic hepatitis B virus infection.Am J Med 2008;121:S45-52.

6 Sherman M,Shafran S,Burak K,Doucette K,Wong W,Girgrah N,et al.Management of chronic hepatitis B:consensus guidelines.Can J Gastroenterol 2007;21:5C-24C.

7 Zheng JY,Liu ZM,Zhu L.Practice and thought of strengthening training of basic skills in general practitioners[abstract in English].China Higher Med Educ 2010;3:123-125.

8 Liang X,Bi S,Yang W,Wang L,Cui G,Cui F,et al.Evaluation of the impact of hepatitis B vaccination among children born during 1992-2005 in China.J Infect Dis 2009;200:39-47.

9 Alter MJ.Epidemiology and prevention of hepatitis B.Semin Liver Dis 2003;23:39-46.

10 K?se S,Türken M,Cavdar G,Tatar B,Senger SS.Evaluation of vaccination results in high-risk patients included in hepatitis B vaccination program.Hum Vaccin 2010;6:903-905.

11 Tanaka M,Katayama F,Kato H,Tanaka H,Wang J,Qiao YL,et al.Hepatitis B and C virus infection and hepatocellular carcinoma in China:a review of epidemiology and control measures.J Epidemiol 2011;21:401-416.

12 Lai CJ,Nguyen TT,Hwang J,Stewart SL,Kwan A,McPhee SJ.Provider knowledge and practice regarding hepatitis B screening in Chinese-speaking patients.J Cancer Educ 2007;22:37-41.

13 Ma GX,Shive SE,Toubbeh JI,Tan Y,Wu D.Knowledge,attitudes,and behaviors of Chinese hepatitis B screening and vaccination.Am J Health Behav 2008;32:178-187.

14 Wu CA,Lin SY,So SK,Chang ET.Hepatitis B and liver cancer knowledge and preventive practices among Asian Americans in the San Francisco Bay Area,California.Asian Pac J Cancer Prev 2007;8:127-134.

15 Hislop TG,Teh C,Low A,Li L,Tu SP,Yasui Y,et al.Hepatitis B knowledge,testing and vaccination levels in Chinese immigrants to British Columbia,Canada.Can J Public Health 2007;98:125-129.

16 Hislop TG,Teh C,Low A,Tu SP,Yasui Y,Coronado GD,et al.Predisposing,reinforcing and enabling factors associated with hepatitis B testing in Chinese Canadians in British Columbia.Asian Pac J Cancer Prev 2007;8:39-44.

17 Thompson MJ,Taylor VM,Yasui Y,Hislop TG,Jackson JC,Kuniyuki A,et al.Hepatitis B knowledge and practices among Chinese Canadian women in Vancouver,British Columbia.Can J Public Health 2003;94:281-286.

18 Coronado GD,Taylor VM,Tu SP,Yasui Y,Acorda E,Woodall E,et al.Correlates of hepatitis B testing among Chinese Americans.J Community Health 2007;32:379-390.

19 Tu R SP,Li L,Tsai JH,Yip MP,Terasaki G,Teh C,et al.A cross-border comparison of hepatitis B testing among chinese residing in Canada and the United States.Asian Pac J Cancer Prev 2009;10:483-490.

20 Nguyen TT,Taylor V,Chen MS Jr,Bastani R,Maxwell AE,McPhee SJ.Hepatitis B awareness,knowledge,and screening among Asian Americans.J Cancer Educ 2007;22:266-272.

21 Li D,Tang T,Patterson M,Ho M,Heathcote J,Shah H.The impact of hepatitis B knowledge and stigma on screening in Canadian Chinese persons.Can J Gastroenterol 2012;26:597-602.

22 Juon HS,Park BJ.Effectiveness of a culturally integrated liver cancer education in improving HBV knowledge among Asian Americans.Prev Med 2013;56:53-58.

23 Hwang JP,Roundtree AK,Engebretson JC,Suarez-Almazor ME.Medical care of hepatitis B among Asian American populations:perspectives from three provider groups.J Gen Intern Med 2010;25:220-227.

24 Takahashi LM,Kim AJ,Sablan-Santos L,Quitugua LF,Aromin J,Lepule J,et al.Hepatitis B among Pacific Islanders in Southern California:how is health information associated with screening and vaccination? J Community Health 2011;36:47-55.

25 Maloy SA.How to reduce hepatitis B in the workplace.The China Business Review [cited 2013 Dec 28].Available from:http://www.chinabusinessreview.com/how-to-reduce-hepatitisb-in-the-workplace/.

26 Juan S.Hepatitis B tests for jobs set to stop.China Daily [cited 2013 Dec 28].Available from:http://www.chinadaily.com.cn/cndy/2009-12/30/content_9244197.htm.

27 Dai XW,Ren JJ,Yao J.Study on hepatitis B vaccination in adults [abstract in English].Zhejiang J Prev Med 2012;11:13-16.

28 Zhu L,Zhai X,Zhu Y,Xu W,Bao C,Peng H,et al.Evaluation of the impact of hepatitis B vaccination in adults in Jiangsu province,China.PLoS One 2014;9:e101501.

29 Advisory Committee on Immunization Practices; Centers for Disease Control and Prevention (CDC).Immunization of health-care personnel:recommendations of the Advisory Committee on Immunization Practices (ACIP).MMWR Recomm Rep 2011;60:1-45.

30 Centers for Disease Control and Prevention.Recommended adult immunization schedule-United States,2013.J Midwifery Womens Health 2013;58:215-220.

31 Yang SG,Wang B,Chen P,Yu CB,Deng M,Yao J,et al.Effectiveness of HBV vaccination in infants and prediction of HBV prevalence trend under new vaccination plan: findings of a large-scale investigation.PLoS One 2012;7:e47808.

32 Ren JJ.Immunological effects of 60 μg/dose hepatitis B vaccine in adults and effects of general practitioners on the prevention and control of hepatitis B.Hangzhou:Zhejiang University; 2013.

33 Mast EE,Weinbaum CM,Fiore AE,Alter MJ,Bell BP,Finelli L,et al.A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States:recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II:immunization of adults.MMWR Recomm Rep 2006;55:1-33.

34 Shepard CW,Simard EP,Finelli L,Fiore AE,Bell BP.Hepatitis B virus infection:epidemiology and vaccination.Epidemiol Rev 2006;28:112-125.

35 Merican I,Guan R,Amarapuka D,Alexander MJ,Chutaputti A,Chien RN,et al.Chronic hepatitis B virus infection in Asian countries.J Gastroenterol Hepatol 2000;15:1356-1361.

36 Mast EE,Margolis HS,Fiore AE,Brink EW,Goldstein ST,Wang SA,et al.A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States:recommendations of the Advisory Committee on Immunization Practices (ACIP) part I:immunization of infants,children,and adolescents.MMWR Recomm Rep 2005;54:1-31.

37 Chen DS.Toward elimination and eradication of hepatitis B.J Gastroenterol Hepatol 2010;25:19-25.

38 Lu J,Xu A,Wang J,Zhang L,Song L,Li R,et al.Direct economic burden of hepatitis B virus related diseases:evidence from Shandong,China.BMC Health Serv Res 2013;13:37.

39 European Association For The Study Of The Liver.EASL clinical practice guidelines:Management of chronic hepatitis B virus infection.J Hepatol 2012;57:167-185.

40 Ma ZX,Li L.Research on prevention and control of hepatitis B and progress of related test index [abstract in English].Int J Lab Med 2011;32:1332-1335.

41 Xu W Su LQ,Li HJ.Advances and clinical evaluation of drugs for hepatitis B [abstract in English].Chin Hosp Pharm J 2008;28:737-739.

42 Zhang S,Feng S,Jin GH,Lu XQ,Du J,Fan XL,et al.Community management of chronic hepatitis B:A qulitative study [abstract in English].Chin Gen Pract 2012;15:733-736.

43 Sun YF,Yang YH,Wu HZ.Main problems of community health service development in new stage [abstract in English].Chin Primary Health Care 2009;1:361.

44 Chao J,Chang ET,So SK.Hepatitis B and liver cancer knowledge and practices among healthcare and public health professionals in China:a cross-sectional study.BMC Public Health 2010;10:98.

45 Wang DY.Advances and practice in the standard treatment of hepatitis B [abstract in English].Modern Pract Med 2010;22:5-6.

46 Yao GB.Importance of perinatal versus horizontal transmission of hepatitis B virus infection in China.Gut 1996;38:S39-42.

47 Chinese Society of Hepatology,CMA.Chronic hepatitis B prevention and treatment guidelines (2010 update).J Exp Clin Infect Dis (electronic edition) 2011;1:79-100.

48 Zhou Y,Wang BH.Status of introducing and stabilizing general practitioners in Community Health Service Organization[abstract in English].Chin Gen Prac 2010;13:697-701.